Infantile and accommodative esotropia (ET) affect 2-3% of children in the U.S. Infantile and accommodative ET disrupt binocular visual experience during the first years of life and may cause amblyopia and severe and permanent impairment of stereoacuity. Amblyopia can be treated but, due to recurrence and persistence of residual amblyopia, it remains the most common form of monocular visual impairment in young adults. Our collaborative research group is now poised to address three critical issues. Aim 1: Current consensus on infantile and accommodative ET is that that early detection and prompt intervention to realign the visual axes can preserve normal stereoacuity. However, our recent work challenges the accepted paradigm and has led us to hypothesize that a congenital deficit in disparity sensitivity is present in the central visual field. We propose to use stereo VEPs, disparity vergence, and accommodative disparity vergence to examine an alternative hypothesis for the first time - that there is a congenital defect in disparity sensitivity in the central 4 i infants with infantile ET and in a large subset of children with accommodative ET. These studies will give us a new, broad understanding of binocular deficits infantile and accommodative ET and have a direct translational impact on the clinical evaluation of the risk/benefits of very earl intervention. Aim 2: It is unknown why some children with ET alternate fixation and avoid amblyopia while others develop a preference for one eye and amblyopia. Based on data from primate models of amblyopia and visual evoked potential data on suppression in amblyopic infants and adults, our hypothesis is that asymmetry in suppressive binocular cortical interactions may predispose some esotropic infants and children to develop amblyopia. In addition, we hypothesize that persistent residual amblyopia despite prolonged or repeated treatment is due to the presence of strong asymmetry in suppressive binocular interactions that fails to diminish with occlusion therapy. We propose to use a novel method that allows us to quantify suppressive interactions to determine whether asymmetries in suppression precede amblyopia, whether these asymmetries resolve when treatment is effective, and whether persistent and recurrent amblyopia result from persistent asymmetric suppression. Aim 3: In a unique approach to determining the visual signal that guides emmetropization, we will utilize an infant cohort that shares the distribution of initial refractive errors of normal infants but failsto undergo emmetropization during the first year of life; i.e., infants with infantile esotropia. This approach will be used to identify the missing visually guided mechanism that normally stimulates axial growth to reduce infantile hyperopia. In a prospective evaluation of a preschool/school-age infantile ET cohort, we will, for the first time, examine the influence of axil and peripheral refractive error, accommodation, and ocular shape on the onset and progression of myopic axial growth in school-age children whose emmetropization had previously been inhibited. PUBLIC HEALTH RELEVANCE: Infantile and accommodative esotropia affect 2-3% of children and can cause permanent visual deficits despite prolonged or repeated treatment with eye patches, glasses, and/or surgery. Thus, the lifelong burden of visual impairment, emotional distress, and financial costs associated with infantile and accommodative ET are considerable. The goal of the project is to understand the roles of abnormal visual experience and congenital factors in leading to these visual deficits in order to facilitate the development of more effectiv prevention and treatment strategies.